This study explores the pathogenesis of otitis media with effusion (OME) and assesses the contribution of the various risk factors including infection, especially viral, allergy and immune competence. Experimental URI using rhinovirus (RV-39) and influenza A virus (IFA) were induced in normal susceptible human volunteers with and without a history of allergic rhinitis. Eustachian tube dysfunction was induced in 70 to 80% of infected subjects for both viruses with OME in 3% of RV-39 and 20% of IFA infected subjects. Enhanced serum IgE synthesis and WBC histamine release was documented in allergic but not in non-allergic subjects; whereas both groups had enhanced cytokines (IL-6, 8 and 10) in nasal secretions.